Daniel J Birmingham1, Joshua E Bitter2, Ezinne G Ndukwe2, Sarah Dials2, Terese R Gullo2, Sara Conroy3, Haikady N Nagaraja3, Brad H Rovin2, Lee A Hebert2. 1. Department of Medicine and Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio; and dan.birmingham@osumc.edu. 2. Department of Medicine and Davis Heart and Lung Research Institute, Ohio State University Medical Center, Columbus, Ohio; and. 3. Division of Biostatistics, Ohio State University College of Public Health, Columbus, Ohio.
Abstract
BACKGROUND AND OBJECTIVES: Autoantibodies to complement C1q (anti-C1q) are associated with the diagnosis of lupus nephritis. In this study, we compare anti-C1q IgG with another complement autoantibody, anti-C3b IgG, as a biomarker of lupus nephritis and lupus nephritis flare. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our investigation involved the Ohio SLE Study, a prospective observational cohort of patients with recurrently active lupus who were followed bimonthly. Serum anti-C1q and anti-C3b IgG levels were assessed cross-sectionally by ELISA in 40 normal controls and 114 patients in the Ohio SLE Study (41 nonrenal and 73 lupus nephritis) at study entry, and longitudinally in a subset of patients in the Ohio SLE Study with anti-C1q-positive lupus nephritis in samples collected every 2 months for 8 months leading up to lupus nephritis flare (n=16 patients). RESULTS: In the cross-sectional analysis, compared with anti-C1q IgG, anti-C3b IgG was less sensitive (36% versus 63%) but more specific (98% versus 71%) for lupus nephritis. Only anti-C3b IgG was associated with patients with lupus nephritis who experienced at least one lupus nephritis flare during the Ohio SLE Study period (P<0.01). In the longitudinal analysis, circulating levels of anti-C1q IgG increased at the time of lupus nephritis flare only in patients who were anti-C3b positive (P=0.02), with significant increases occurring from 6 (38% increase) and 4 months (41% increase) before flare. Anti-C3b IgG levels also trended up at lupus nephritis flare, although the change did not reach statistical significance (P=0.07). Neither autoantibody increased 2 months before flare. CONCLUSIONS: Although not as prevalent as anti-C1q IgG, anti-C3b IgG showed nearly complete specificity for lupus nephritis. The presence of anti-C3b IgG identified patients with lupus nephritis who were prone to flare and in whom serial measurements of markers associated with complement, such as anti-C1q IgG, may be useful to monitor lupus nephritis activity.
BACKGROUND AND OBJECTIVES: Autoantibodies to complement C1q (anti-C1q) are associated with the diagnosis of lupus nephritis. In this study, we compare anti-C1q IgG with another complement autoantibody, anti-C3b IgG, as a biomarker of lupus nephritis and lupus nephritis flare. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our investigation involved the Ohio SLE Study, a prospective observational cohort of patients with recurrently active lupus who were followed bimonthly. Serum anti-C1q and anti-C3b IgG levels were assessed cross-sectionally by ELISA in 40 normal controls and 114 patients in the Ohio SLE Study (41 nonrenal and 73 lupus nephritis) at study entry, and longitudinally in a subset of patients in the Ohio SLE Study with anti-C1q-positive lupus nephritis in samples collected every 2 months for 8 months leading up to lupus nephritis flare (n=16 patients). RESULTS: In the cross-sectional analysis, compared with anti-C1q IgG, anti-C3b IgG was less sensitive (36% versus 63%) but more specific (98% versus 71%) for lupus nephritis. Only anti-C3b IgG was associated with patients with lupus nephritis who experienced at least one lupus nephritis flare during the Ohio SLE Study period (P<0.01). In the longitudinal analysis, circulating levels of anti-C1q IgG increased at the time of lupus nephritis flare only in patients who were anti-C3b positive (P=0.02), with significant increases occurring from 6 (38% increase) and 4 months (41% increase) before flare. Anti-C3b IgG levels also trended up at lupus nephritis flare, although the change did not reach statistical significance (P=0.07). Neither autoantibody increased 2 months before flare. CONCLUSIONS: Although not as prevalent as anti-C1q IgG, anti-C3b IgG showed nearly complete specificity for lupus nephritis. The presence of anti-C3b IgG identified patients with lupus nephritis who were prone to flare and in whom serial measurements of markers associated with complement, such as anti-C1q IgG, may be useful to monitor lupus nephritis activity.
Authors: Leendert A Trouw; Tom W L Groeneveld; Marc A Seelen; Jacques M G J Duijs; Ingeborg M Bajema; Frans A Prins; Uday Kishore; David J Salant; J Sjef Verbeek; Cees van Kooten; Mohamed R Daha Journal: J Clin Invest Date: 2004-09 Impact factor: 14.808
Authors: Daniel J Birmingham; Michael Merchant; Sushrut S Waikar; Haikady Nagaraja; Jon B Klein; Brad H Rovin Journal: Nephrol Dial Transplant Date: 2017-01-01 Impact factor: 5.992
Authors: Maria Chiara Marinozzi; Lubka T Roumenina; Sophie Chauvet; Alexandre Hertig; Dominique Bertrand; Jérome Olagne; Marie Frimat; Tim Ulinski; Georges Deschênes; Stephane Burtey; Michel Delahousse; Bruno Moulin; Christophe Legendre; Véronique Frémeaux-Bacchi; Moglie Le Quintrec Journal: J Am Soc Nephrol Date: 2017-01-17 Impact factor: 10.121
Authors: Marva M Moxey-Mims; Michael F Flessner; Lawrence Holzman; Frederick Kaskel; John R Sedor; William E Smoyer; Aliza M Thompson; Lynne Yao Journal: Clin J Am Soc Nephrol Date: 2016-09-26 Impact factor: 8.237